Analysis of carcinogenesis in hepatocellular carcinoma using Nrf2-p62 double knock out mouse

2017 Fiscal Year Final Research Report

• Project/Area Number: 15H04917
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: University of Tsukuba
• Principal Investigator: YANAGAWA Toru 筑波大学, 医学医療系, 准教授 (10312852)
• Co-Investigator(Kenkyū-buntansha): 田渕 克彦 信州大学, 学術研究院医学系, 教授 (20546767) ; 蕨 栄治 筑波大学, 医学医療系, 講師 (70396612) ; 内田 文彦 筑波大学, 附属病院, 医員 (70736008)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: p62 / Nrf2

Outline of Final Research Achievements

We generated Nrf2-p62 double knock out mouse. Nrf2 is a transcription factor against oxidative stress . p62 is a substrate of selective autophagy. The liver of this mouse showed at first NAFLD and NASH, then finally turn into hepatocellular carcinoma. We found p62 deficient MEF showed resistance to apoptosis. Nrf2-p62 DKO cell showed reduction of phagocytic capacity of hepatic Kupffer cell (macrophage). By using clinical samples, immunohistochemical analysis of p62、LC3-A・B expression in normal tissue with carcinoma was performed. The p62、LC3-A・B expression group showed significantly poor prognosis analyzed by Kaplan mere curve and log rank test. The LC3-A・B expression group showed significantly poor prognosis analyzed by Cox's proportional hazard regression model. From above results we discussed the cause of carcinogenesis of hepatocellular carcinoma by p62 deficiency and oxidative stress accumulation.

Free Research Field

外科学